VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 231

transfer for imaging and therapy (Hajitou et al ., 2006b; Trepel et al ., 2009).

In short, the AAV genome was genetically modified with various reporter
gene cassettes (a reporter gene encodes a marker that is easily detectable,
such as fluorescent proteins), incorporated into the fd phage genome,
and packaged into the bacteriophage. To facilitate targeting of cancer
cells and endothelium, the well-established RGD motif was utilized on the
bacteriophage exterior. Ligand-directed internalization, and transfer and
expression of the reporter genes were demonstrated

in vivo.
Tissue specificity and efficiency of gene delivery and expression post-
systemic administration was confirmed using several tumor mouse models
(Hajitou

in vitro and

imaging of reporter genes
was performed using bioluminescence imaging and PET (Fig. 8.11). To
test the therapeutic potential of the vector, suicide genes were delivered;
transgene expression was found to be indeed sufficiently high for effective
tumor treatment (Fig. 8.11) (Hajitou

et al ., 2006b; Trepel et al ., 2009). In vivo

., 2006b). This study clearly
highlights the potential of viral nanotechnology for the development of novel
imaging modalities and/or therapies.
In another example, VLPs from the bacteriophage MS2 were engineered

et al

′

to package anti-sense RNA against the 5 -untranslated region and

internal ribosome entry site of the (HCV). Packaging was

accomplished by fusion of the anti-sense RNA sequence to the stem loop
triggering encapsulation (recall Section 5.1.1). Cell delivery and penetration
was achieved making use of cell-penetrating peptides that were chemically
attached to surface Lys side chains present on the VLP. Inhibitory effects
on gene expression of HCV were shown

Hepatitis C virus

in vitro using an established

reporter system (Wei ., 2009). The utility of non-human pathogens

as viral vectors for gene or RNAi delivery opens a new sector in viral
nanotechnology. Future studies evaluating transfection efficiency as well as
non-desired side effects comparing non-human viral vectors, viral vectors,
and non-viral delivery systems are expected to give further insights into the
feasibility of utilizing non-human VLPs for gene delivery.

et al

. Future dIreCtIonS

Recent advances in nanotechnology have led to the development of VNPs and
VLPs for potential applications as vaccines, imaging modalities, and targeted
therapeutic devices. The vast majority of studies conducted so far, however,
are on a biochemical level or in tissue culture in vitro . Only a few systems

have been evaluated performance

of specifically engineered and designed VNPs is limited. Studies reported

in vivo , and information on the in vivo